# Molecular mechanisms of post-transplant recurrent alcoholic liver disease

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $110,279

## Abstract

PROJECT SUMMARY
 This proposal outlines a plan to investigate the role of ceramides in alcohol-induced lipid droplet
biogenesis and in post-liver transplant alcoholic liver disease (ALD) recurrence. The research will use novel in
vitro and in vivo model systems to investigate the hypothesis that the ceramide synthetic enzyme ceramide
synthase 6 (CerS6) regulates alcohol-induced lipid droplet biogenesis through the transcriptional regulation of
the lipid droplet protein, Perilipin 2 (PLIN2). Furthermore, this proposal will investigate the association between
CerS6 upregulation in alcoholic steatosis and graft loss in post-transplant recurrent ALD. The researcher aims
1) to determine the mechanisms by which CerS6 regulates PLIN2 and lipid droplet biogenesis; 2) to
determine the effects of hepatocyte-specific CerS6 ablation on lipid and glucose homeostasis in
experimental ALD and 3) to determine if CerS6 expression predicts graft loss in post-transplant
recurrent ALD.
 To accomplish these Specific Aims, the researcher proposes to use CRISPR/Cas9 genetically
engineered mice and human ethanol-metabolizing VL17A cells to perform comprehensive metabolic
phenotyping, lipidomics analyses, and biochemical and functional assays. In addition, the researcher aims to
examine if CerS6 immunohistochemical expression predicts graft loss in patients with recurrent ALD post-
transplant. Results of this project will provide evidence for targeting CerS6 as a diagnostic and therapeutic
biomarker in post-transplant ALD recurrence.

## Key facts

- **NIH application ID:** 10174616
- **Project number:** 5R01AA026302-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** ROTONYA M CARR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $110,279
- **Award type:** 5
- **Project period:** 2017-09-10 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174616

## Citation

> US National Institutes of Health, RePORTER application 10174616, Molecular mechanisms of post-transplant recurrent alcoholic liver disease (5R01AA026302-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10174616. Licensed CC0.

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